Blood feeding (hemophagic) arthropod pests are of great concern not only because of their annoying and often painful bites, but more importantly because many can also be vectors (carriers) of pathogenic (disease causing) organisms, that seriously injure or kill humans and domestic animals, e.g., encephalitis, tularema, Lyme disease, malaria, yellow fever, Chagas disease, bubonic plague, murine typhus, tapeworms, Rocky Mountain fever, etc.
Trypanosoma cruzi causes Chagas disease in humans. Acute infection can be lethal, but the disease usually evolves into a chronic stage, accompanied in 25-30% of cases by severe debilitation and ultimately death. It is estimated that 16-18 million people are infected, primarily in Central and South America, with 21,000 deaths reported each year.
Trypanosoma cruzi exists in four morphologically and biologically distinct forms during its cycle of development in mammals and insects: metacyclic trypomastigotes, amastigotes, trypomastigotes and epimastigotes (FIG. 1). The amastigote and trypomastigote stages are sometimes referred to as the “mammalian stages,” and the metacyclic trypomastigote and epimastigote stages are sometimes referred to as the “insect stages.” Metacyclic trypomastigotes develop in the hind gut of triatomine insect vectors and initiate infection in a wide variety of animal species, including humans. T. cruzi trypomastigotes are normally transmitted from the reduviid bug to the mammalian host via the vector feces after a bug bite, but also by ingestion of contaminated food, or following blood transfusion or organ donation. Trypomastigotes can invade several types of host cells. In host cells trypomastigotes convert to replicative aflagellate amastigote forms which reside in the host cell cytoplasm. Following multiple rounds of binary fission, the aflagellate amastigotes convert into non-dividing flagellated trypomastigotes that burst from the host cell and circulate in the bloodstream. The extracellular trypomastigotes can initiate another round of host cell infection, invading other host cells and thus spread the infection throughout the body. Alternatively, trypomastigotes acquired by a reduviid vector during a blood meal convert to epimastigote forms, which replicate in the insect gut before eventually differentiating into infective metacyclic trypomastigote forms.
The bulk of human transmission of T. cruzi is a consequence of infestation of sub-standard housing by T. cruzi-infected reduviid bugs wherein these insects feed on the inhabitants that generally include not only humans but also dogs and other pets and livestock animals. Field and modeling studies suggest that dogs in particular are the major reservoir for T. cruzi in most houses and most insects become infected, and thus capable of transmitting infection to humans, by feeding on T. cruzi infected dogs (Cohen et al., Science. 2001 Jul 27; 293(5530):694-8).
Historical attempts to develop vaccines for parasitic diseases have been largely futile, and there is a critical lack of methods for diagnosis and treatment for T. cruzi in particular. Improved drugs and vaccines for the treatment and prevention of T. cruzi infection are needed, as are improved diagnostic methods.